2-(4-Amino-3-fluoro-phenoxy)-2-methyl-propionic acid ethyl ester → 2-(4-{2-[2-(4-Chloro-phenyl)-2,4,5,6,7,8-hexahydro-cycloheptapyrazol-3-yl]-2-cyclohexyl-acetylamino}-3-fluoro-phenoxy)-2-methyl-propionic acid ethyl ester

Participants

Reaction Steps

A solution of [2-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-cycloheptapyrazol-3-yl]-cyclohexyl-acetic acid (40 mg, 103 umol) in thionyl chloride (2 ml) was heated under reflux conditions for 45 min. The solvent was removed under reduced pressure and the resulting crude [2-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-cycloheptapyrazol-3-yl]-cyclohexyl-acetyl chloride was dissolved in CH2Cl2 (1 ml) and added to a solution of 2-(4-amino-3-fluoro-phenoxy)-2-methyl-propionic acid ethyl ester (37 mg, 155 umol) and DMAP (38 mg, 310 umol) in CH2Cl2 (1 ml). The reaction mixture was stirred at ambient temperature for 14 h. Ice water/brine 1/1 was added and the mixture was extracted two times with iPrOAc. The combined extracts were washed with ice water/brine 1/1 and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a brown oil which was purified by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water to obtain the title compound (15 mg, 25 umol; 24%) as brown solid. MS: m/e=610.3 [M+H+].

Provenance & Evidence